Does solid culture for tuberculosis influence clinical decision making in India?

Stall, Nathan M.; Rubin, Tamar; Js, Michael; Mathai, Dilip; Oc, Abraham; Mathews, Paul M.; Thomas, Kristen; John, Melanie-Anne; Daley, Peter

doi:10.5588/ijtld.10.0195

Cited by 16 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our analysis suggests that enhanced laboratory identification using solid culture media and blood culture averted, at most, eight additional TB deaths implying that solid TB culture, even if routinely available, may offer only modest gains, a conclusion also reported from India [37]. Prompt initiation of TB treatment would be better supported through improved access to rapid point-of-care diagnostics for TB but in their absence empiric TB treatment warrants careful consideration, particularly among patients with the risk factors for mortality observed in this study.…”

Section: Discussionsupporting

confidence: 62%

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi

Lettow

Åkesson²,

Martiniuk

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

BackgroundIn sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy.MethodsA prospective cohort study was conducted in Malawi, investigating mortality in relation to ART uptake, microbiological findings and treatment of opportunistic infection (OIs), 6 months after meeting ART eligibility criteria.ResultsOf 469 consecutive adults eligible for ART, 74(16%) died within 6 months of enrolment, at a median of 41 days (IQR 20–81). 370(79%) started ART at a median time of 18 days (IQR 7–40) after enrolment. Six-month case-fatality rates were higher in patients with OIs; 25/121(21%) in confirmed/clinical TB and 10/50(20%) with blood stream infection (BSI) compared to 41/308(13%) in patients with no infection identified. Median TB treatment start was 27 days (IQR 17–65) after enrolment and mortality [8 deaths (44%)] was significantly higher among 18 culture-positive patients with delayed TB diagnosis compared to patients diagnosed clinically and treated promptly with subsequent culture confirmation [6/34 (18%);p = 0.04]. Adjusted multivariable analysis, excluding deaths in the first 21 days, showed weight loss >10%, low CD4 count, severe anemia, laboratory-only TB diagnosis, and not initiating ART to be independently associated with increased risk of death.ConclusionsMortality remains high among chronically ill patients eligible for ART. Prompt initiation of ART is vital: more than half of deaths were among patients who never started ART. Diagnostic and treatment delay for TB was strongly associated with risk of death. More than half of deaths occurred without identification of a specific infection. ART programmes need access to rapid point-of-care-diagnostic tools for OIs. The role of early empiric OI treatment in this population requires further evaluation in clinical trials.

show abstract

Section: Discussionsupporting

confidence: 62%

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi

Lettow

Åkesson²,

Martiniuk

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…We were unable to compute numeric differences in the estimates of meta-analyses versus package inserts because pooling of data was often not possible due to heterogeneity between studies and the presence of several meta-analyses that included partially overlapping studies. We acknowledge that real-world performance of tests, especially when tests are scaled up in public health programs, may be worse than those reported in research studies, including meta-analyses (27). Thus, the real gap between package insert estimates and real-world performance may be even wider than what we document here.…”

contrasting

confidence: 50%

Promise versus Reality: Optimism Bias in Package Inserts for Tuberculosis Diagnostics

et al. 2012

View full text Add to dashboard Cite

e Laboratorians and clinicians often rely on package inserts of diagnostic tests to assess their accuracy. We compared test accuracy for tuberculosis diagnostics reported in 19 package inserts against estimates in published meta-analyses and found that package inserts generally report overoptimistic accuracy estimates. However, package inserts of most tests approved by the U.S. Food and Drug Administration (FDA) or endorsed by the World Health Organization provide more realistic estimates that agree with meta-analyses. Most laboratory professionals anticipate that test performance when applied to patient care may be less impressive than what is reported in package inserts by test manufacturers. However, this gap between promise and reality has not been examined in a systematic way.One approach for studying this gap is to compare sensitivity and specificity estimates in package inserts with pooled estimates from published systematic reviews and meta-analyses, which often include studies from diverse settings and may provide a more realistic assessment of test accuracy.We conducted such a comparison using commercial tuberculosis (TB) diagnostics as a case study. The TB diagnostic pipeline has rapidly expanded, and a large number of meta-analyses have been published on various TB tests (24). Several tests are now endorsed by the World Health Organization (WHO). At the same time, there are examples of suboptimal and inaccurate TB diagnostic tests, and their use has been discouraged by the WHO (32). In fact, in vitro tests are often poorly regulated in many countries (13).We searched PubMed, the Cochrane Library, and the Evidence-Based TB Diagnosis website (www.tbevidence.org) for systematic reviews on the accuracy of diagnostics for TB published through March 2012 (search terms are available from the authors upon request). We excluded meta-analyses that reported only performance characteristics other than sensitivity and specificity (e.g., reproducibility, likelihood ratios), as they were not comparable to information provided in package inserts.We searched company websites for package inserts and contacted test manufacturers if package inserts were not available online. Diagnostic tests were not considered if they were not commercially available. Diagnostic tests for latent TB were not considered, because no good reference standard is available to determine accuracy.A total of 19 TB tests were included in the final analysis, because they met our eligibility criteria and package inserts as well as meta-analyses where available. These included gamma interferon (IFN-␥) release assays (IGRAs) for active TB, antibody-based serological tests, antigen detection tests, nucleic acid amplification tests (NAAT), and culture-based tests.As seen in Table 1, the quality of information provided in package inserts varies widely. Eighteen out of 19 package inserts in total overestimated the test accuracy. In particular, technologies that were neither recommended by the WHO nor approved by the U.S. Food and Drug Administration (FDA)...

show abstract

“…In addition to smear, IGRA, and Xpert MTB/RIF, we also examined a scenario including mycobacterial culture. We do not present those findings in detail, however, as research has shown that culture results have limited impact on physician’s treatment decisions in India [ 19 ]. We included the effects of multi-drug resistant TB (MDR-TB) on each these diagnostic scenarios, assuming an MDR-TB prevalence of 2.1% among all newly diagnosed Indian adult TB cases [ 20 ], and examined the costs and consequences of diagnosing and treating MDR-TB for the Xpert arm (as, unlike smear or IGRA, Xpert is capable of diagnosing resistance to rifampin, a proxy measure for MDR-TB).…”

Section: Methodsmentioning

confidence: 96%

Costs and Consequences of Using Interferon-γ Release Assays for the Diagnosis of Active Tuberculosis in India

2015

View full text Add to dashboard Cite

BackgroundThere is growing concern that interferon-γ release assays (IGRAs) are being used off-label for the diagnosis of active tuberculosis (TB) disease in many high-burden settings, including India, where the background prevalence of latent TB infection is high. We analyzed the costs and consequences of using IGRAs for the diagnosis of active TB in India from the perspective of the Indian TB control sector.Methods and FindingsWe constructed a decision analytic model to estimate the incremental cost and effectiveness of IGRAs for the diagnosis of active TB in India. We compared a reference scenario of clinical examination and non-microbiological tests against scenarios in which clinical diagnosis was augmented by the addition of either sputum smear microscopy, IGRA, or Xpert MTB/RIF. We examined costs (in 2013 US dollars) and consequences from the perspective of the Indian healthcare sector. Relative to sputum smear microscopy, use of IGRA for active TB resulted in 23,700 (95% uncertainty range, UR: 3,800 – 38,300) additional true-positive diagnoses, but at the expense of 315,700 (95% UR: 118,300 – 388,400) additional false-positive diagnoses and an incremental cost of US$49.3 million (95% UR: $34.9 – $58.0 million) (2.9 billion Indian Rupees). Relative to Xpert MTB/RIF (including the cost of treatment for drug resistant TB), use of IGRA led to 400 additional TB cases treated (95% UR: [-8,000] – 16,200), 370,600 (95% UR: 252,200 – 441,700) more false-positive diagnoses, 70,400 (95% UR: [-7,900] – 247,200) fewer disability-adjusted life years averted, and US$14.6 million (95%UR: [-$7.2] – $28.7 million) (854 million Indian Rupees) in additional costs.ConclusionUsing IGRAs for diagnosis of active TB in a setting like India results in tremendous overtreatment of people without TB, and substantial incremental cost with little gain in health. These results support the policies by WHO and Standards for TB Care in India, which discourage the use of IGRAs for the diagnosis of active TB in India and similar settings.

show abstract

Does solid culture for tuberculosis influence clinical decision making in India?

Abstract: Using solid culture, 150 cultures need to be tested for one treatment modification and 30 for DST. The cost of the widespread application of culture will need to be balanced against its impact on treatment decisions in India.

Cited by 16 publications

References 0 publications

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi

Promise versus Reality: Optimism Bias in Package Inserts for Tuberculosis Diagnostics

Costs and Consequences of Using Interferon-γ Release Assays for the Diagnosis of Active Tuberculosis in India

Contact Info

Product

Resources

About